反应详情

To an ice cooled solution of 1,1-dimethylethyl (3S)-3-fluoro-3-(hydroxymethyl)-1-piperidinecarboxylate (1.406 g, 6.03 mmol) in DMF (20 ml) was added sodium hydride (0.313 g, 7.84 mmol) (60% dispersion in mineral oil). This was stirred for 15 min before adding 5,7-dichloro-1,6-naphthyridine (1.2 g, 6.03 mmol). This was warmed to room temp and stirred for 4 h. The reaction had gone to completion and so was cautiously quenched with aqueous ammonium chloride before partitioning between aqueous ammonium chloride and ethyl acetate. The layers were separated and the aqueous was re-extracted with ethyl acetate. The combined organics were washed with brine and concentrated in vacuo to give the crude product. This was dissolved in DCM and purified through silica (50 g), eluting with a gradient of 0-50% ethyl acetate in DCM. Appropriate fractions were concentrated in vacuo to yield the title compound as a cream foamy gum (1.91 g).

1. stirringstirred for 4 h
2. customso was cautiously quenched with aqueous ammonium chloride
3. custombefore partitioning between aqueous ammonium chloride and ethyl acetate
4. customThe layers were separated
5. extractionthe aqueous was re-extracted with ethyl acetate
6. washThe combined organics were washed with brine
7. concentrationconcentrated in vacuo
8. customto give the crude product
9. custompurified through silica (50 g)
10. washeluting with a gradient of 0-50% ethyl acetate in DCM
11. concentrationAppropriate fractions were concentrated in vacuo